7-135571368-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015135.3(NUP205):c.171+121C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0172 in 572,154 control chromosomes in the GnomAD database, including 267 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.026 (87 hom., cov: 29)
  • Exomes 𝑓: 0.014 (180 hom.)
• Consequence: NUP205 NM_015135.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.375

Genes affected

NUP205 (HGNC:18658): (nucleoporin 205) This gene encodes a nucleoporin, which is a subunit of the nuclear pore complex that functions in active transport of proteins, RNAs and ribonucleoprotein particles between the nucleus and cytoplasm. Mutations in this gene are associated with steroid-resistant nephrotic syndrome. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BP6: Variant 7-135571368-C-A is Benign according to our data. Variant chr7-135571368-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1317650.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0963 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUP205	NM_015135.3	c.171+121C>A		intron_variant		ENST00000285968.11
NUP205	NM_001329434.2	c.-915+121C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUP205	ENST00000285968.11	c.171+121C>A		intron_variant		1	NM_015135.3	P1
NUP205	ENST00000489493.1	n.426+121C>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0263 AC: 3834 AN: 145648 Hom.: 87 Cov.: 29

Gnomad AFR AF: 0.0499

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0130

Gnomad ASJ AF: 0.0230

Gnomad EAS AF: 0.0574

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.00101

Gnomad MID AF: 0.0161

Gnomad NFE AF: 0.0119

Gnomad OTH AF: 0.0215

GnomAD4 exome AF: 0.0141 AC: 6032 AN: 426438 Hom.: 180 AF XY: 0.0150 AC XY: 3249 AN XY: 216998

Gnomad4 AFR exome AF: 0.0359

Gnomad4 AMR exome AF: 0.00766

Gnomad4 ASJ exome AF: 0.0177

Gnomad4 EAS exome AF: 0.0579

Gnomad4 SAS exome AF: 0.0643

Gnomad4 FIN exome AF: 0.00171

Gnomad4 NFE exome AF: 0.00913

Gnomad4 OTH exome AF: 0.0172

GnomAD4 genome AF: 0.0263 AC: 3833 AN: 145716 Hom.: 87 Cov.: 29 AF XY: 0.0277 AC XY: 1953 AN XY: 70494

Gnomad4 AFR AF: 0.0499

Gnomad4 AMR AF: 0.0129

Gnomad4 ASJ AF: 0.0230

Gnomad4 EAS AF: 0.0572

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.00101

Gnomad4 NFE AF: 0.0119

Gnomad4 OTH AF: 0.0208

Alfa AF: 0.00335 Hom.: 0

Bravo AF: 0.0279

Asia WGS AF: 0.0870 AC: 300 AN: 3468

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 03, 2020

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.52
Dann	Benign	0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs74661631; hg19: chr7-135256116;